A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix.

A positively thermosensitive drug-release microcapsule (MC) with diameter around 100 microm was designed and its preparation was carried out by using an air suspension coating technique (the Wurster process). The MC had a core layered with carbazochrome sodium sulfonate (CCSS, a water-soluble model drug) particles and a thermosensitive coat composed of an ethylcellulose matrix containing nano-sized thermosensitive hydrogels. The hydrogel particles consisted of a newly synthesized composite latex with a poly(N-isopropylacrylamide (NIPAAm)) shell that could reversibly change the shell thickness in water with response to an environmental temperature change. This MC demonstrated a positively thermosensitive drug release: the release rate was remarkably enhanced at temperatures above a lower gel collapse point (temperature for complete deswelling) of 32 degrees C, suggesting that the shrinkage of poly(NIPAAm) shells most likely created many voids in the coat and thereby imparted the higher water-permeability to the coat. Thermosensitivity of drug release highly depended on the composite latex particle content in the coat. It became most distinct when its content reached 12.5 and 15 wt%. In addition, it was found that the present MC membrane made it possible to obtain an 'on-off' pulsatile release, which could alter the release rate in the order of a minute, in response to stepwise temperature changes between 30 and 50 degrees C.